Pathogenesis model of stromal reaction in TPO^high mice. TPO overexpression leads to megakaryocyte hyperplasia in hematopoietic tissues with dysmegakaryopoiesis and increases neutrophil emperipolesis, which induces, probably with the contribution of monocytes, an augmentation of the TGF-β1 release in extracellular fluids of bone marrow and spleen. The local activation of TGF-β1 is required within hematopoietic microenvironment for the fibroblast-mediated fibrosis development. Osteosclerosis development is related, on one hand, to osteoblast proliferation stimulated by TGF-β1 and, on the other hand, to the inhibition of osteoclastogenesis mediated by an increased secretion of stromal cell–derived OPG. IL-1α, released by hematopoietic cells, monocytes, and platelets, may be the cytokine responsible of this OPG up-regulation.